Functional evidence that in the cardiovascular system AT angiotensin II receptors are AT prejunctionally and AT postjunctionally

Abstract

Numerous studies have shown that angiotensin II causes vasoconstriction both by a direct action on smooth muscle cells (postjunctional effect) and indirectly through the facilitation of noradrenaline release from postganglionic sympathetic neurons (prejunctional effect). The receptors through which angiotensin II exerts its actions were first divided into AT1 and AT2 subtypes. A further subdivision of AT1 receptors into AT1A and AT1B subtypes was based on cloning and receptor binding studies: AT1A showed a high affinity for losartan, but low affinity for PD123319, while AT1B receptors showed nearly 100-fold lower affinity for losartan and 10,000-fold higher affinity for PD123319 relative to AT1 sites. The present review deals with functional evidence supporting the existence of AT1A and AT1B subtypes in the cardiovascular system. Taken together, all the functional results obtained in vivo and in vitro-in a wide variety of vascular tissues from different species-allow one to conclude that angiotensin II AT1 receptors are different pre- and postjunctionally and also that prejunctional and postjunctional angiotensin II receptors most probably belong to AT1B and AT1A subtypes, respectively.

Developmental Programming Through Epigenetic Changes

“…13 Which AT 1 receptor subtype is upregulated however has not been examined. Reports showing that AT 1b might play a role in vasoconstriction at the pre junctional level (postganglionic sympathetic neurons innervating vascular smooth muscle cells) 14 could support the hypothesis presented by Bogdarina et al of a role for AT 1b in programmed hypertension; however vascular expression of AT 1a versus AT 1b was not examined in this article. 3 AT 1 is responsible for most of the known functions of the renin-angiotensin system in both physiological and pathophysiological conditions: vascular smooth muscle contraction, proliferation of vascular smooth muscle cell, aldosterone release and regulation of fluid electrolyte balance.…”

Effects of the ACE2 inhibitor GL1001 on acute dextran sodium sulfate-induced colitis in mice

“…AT1 receptor stimulation has been associated with vasoconstriction, cell proliferation, hypertrophy, and inflammation. In contrast, AT2 receptor stimulation is believed to mediate nitric oxide release and tissue repair, as well as anti-proliferative and anti-fibrotic effects [9,12,36]. Interestingly, Ang II and various peptide analogues appear to have higher binding affinity for AT2 versus AT1 receptors [37][38][39].…”

Angiotensin II-induced vasodilatation in cerebral arteries is mediated by endothelium-derived hyperpolarising factor

“…In contrast to the angiotensin AT 1A subtype, the angiotensin AT 1B receptor can be inhibited by a high concentration (> 0.5 µM) of PD 123319 (Guimaraes and Pinheiro, 2005). In the present setting, a low concentration of PD 123319 (0.1 µM) was used, only affecting the angiotensin AT 2 receptors.…”

“…There is evidence that angiotensin AT 1B receptors acts indirectly through the facilitation of the exocytic release of noradrenaline from sympathetically innervated tissues, while angiotensin AT 1A receptors acts directly on vascular cells (Guimaraes and Pinheiro, 2005). In the present study, the angiotensin AT 1 receptor effect is most probably mediated by the angiotensin AT 1A receptor subtype, since angiotensin II was administered on the luminal side of the artery to stimulate vascular tissue where mainly angiotensin AT 1A receptors are present (Guimaraes and Pinheiro, 2005). Although, a subdivision into different angiotensin AT 1 receptor subtypes can not be done from the present results.…”